Abstract
Impaired cellular uptake and utilization of glucose is the hallmark of non-insulin-dependent-diabetes (NIDDM). We have developed a quantitative assay to probe the expression of glucose-transporter genes in tissues derived from patients with NIDDM. Using the polymerase chain reaction (PCR), we assessed levels of expression of the insulin responsive glucose transporter GLUT-4 in adipose tissue of patients with NIDDM and in obese patients. We report that expression of GLUT-4 is reduced in NIDDM and in obesity associated with hyperinsulinemia and insulin resistance. These results suggest that reduction of GLUT-4 levels in the adipose cell plays an important role in the pathogenesis of insulin resistance, an early feature of NIDDM.
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Pessin J.E., Bell G.I. Mammalian facilitative glucose transporter family: structure and molecular regulation. Ann. Rev. Physiol. 54: 911, 1992.
DeFronzo R.A., Bonadonna R.C., Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15: 318, 1992.
Berger J., Biswas C., Vicario P.P., Strout H.V., Saperstein R., Pilch P.F. Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting. Nature 340: 70, 1989.
Sivitz W.I., DeSautel S.L., Kayano T., Bell G.I., Pessin J.E. Regulation of glucose transporter messenger RNA in insulin-deficient states. Nature 340: 72, 1989.
Seino Y., Yamamoto T., Koh G. Insulin and glucose transporter gene expression in obesity and diabetes. Proc. Soc. Exp. Biol. Med. 200: 210, 1992.
Pedersen O., Bak J.F., Andersen P.H., Lund S., Moller D.E., Flier J.S., Kahn B.B. Evidence against alterated expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes 39: 865, 1990.
Eriksson J., Koranyi L., Bourey R., Schalin-Jantti C., Widen E., Muecler M., Permutt A.M., Groop L.C. Insulin resistance in type 2 (non-insulin-dependent) diabetic patients and their relatives is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle. Diabetologia 35: 143, 1992.
Garvey W.T., Maianu L., Hancock J.A., Golichowski A.M., Baron A. Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM. Diabetes 41: 465, 1992.
Yki-Jarvien H., Vuorinen-Markkola H., Koranyi L., Bourey R., Tordjman K., Mueckler M., Permutt A.M., Koivisto V.A. Defect in insulin action on expression of the muscle/adipose tussue glucose transport gene in skeletal muscle of type 1 diabetic patients. J. Clin. Endocrinol. Metab. 75: 795, 1992.
Garvey W.T., Maianu L., Huecksteadt T.P., Birnbaum M.J., Molina J.M., Ciaraldi T.P. Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin-dependent diabetes mellitus and obesity. J. Clin. Invest. 87: 1072, 1991.
Chomczynski P., Sacchi N. Single step method of RNA isolation by acid guanidinium thiocyanate phenol chloroform extraction. Anal. Biochem. 162: 156, 1987.
Mueckler M., Caruso C., Baldwin S.A., Panico M., Blench I., Morris H.R., Allard W.J., Lienhard G.E., Lodish H.F. Sequence and structure of a human glucose transporter. Science 229: 941, 1985.
Buse J.B., Yasuda K., Lay T.P., Seo T.S., Olson A.L., Pessin J.E., Karam J.H., Seino S., Bell G.I. Human GLUT4/muscle-fat glucose-transporter gene. Characterization and genetic variation. Diabetes 41: 1436, 1992.
Accili D., Frapier C., Mosthaf L., McKeon C., Elbein S.C., Permutt A., Ramos E., Lander E.S., Ullrich A., Taylor S.I. A mutation of the insulin receptor gene which impairs transport of the receptor to the plasma membrane and causes insulin-resistant diabetes. EMBO J. 8: 2509, 1989.
Accili D., Perrotti N., Rees-Jones R.W., Taylor S.I. Tissue distribution and subcellular localization of an endogenous substrate for the insulin recepter-associated tyrosine kinase. Endocrinology 119: 1274, 1986.
Saiki R.S. The design and optimization of PCR. In: Erlich H.A. (Ed.), PCR Technology. Stockton Press, New York, 1989, p. 7.
Wang A.M., Doyle M.V., Mark D.F. Quantitation of mRNA by the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 86: 9717, 1989.
Katz E.D., DiCesare J.L., Picozza E., Anderson M.S. General aspects of PCR quantitation. Amplifications 10: 7, 1993.
Sivitz W.I., Lee E.C. Assessment of glucose transporter gene expression using the polymerase chain reaction. Endocrinology 128: 2387, 1991.
Choi W.H., O’Rahilly S., Buse J.B., Rees A., Morgan R., Flier J.S., Moller D.E. Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects. Diabetes 40: 1712, 1991.
Kusari J., Verma U.S., Buse J.B., Henry R.R., Olefsky J.M. Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus. J. Clin. Invest. 88: 1323, 1991.
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This work was supported by Grant from Consiglio Nazionale delle Ricerche (Rome, Italy). Target Project: Progetto Finalizzato Invecchiamento (n. 92.00280.PF40) and in part Progetto Finalizzato Fatma
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Giacchetti, G., Faloia, E., Taccaliti, A. et al. Decreased expression of insulin-sensitive glucose transporter mRNA (GLUT-4) in adipose tissue of non-insulin-dependent diabetic and obese patients: Evaluation by a simplified quantitative PCR assay. J Endocrinol Invest 17, 709–715 (1994). https://doi.org/10.1007/BF03347765
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DOI: https://doi.org/10.1007/BF03347765